"You can be cured, but cancer never leaves you behind": an interdisciplinary approach into the embodied cancer experiences among adult Colombian childhood/adolescent cancer survivors.

PURPOSE: Childhood or adolescent cancer survivors (CACS) are an understudied population in Colombia and, in general, in Central and South America. Worldwide, studies typically focus on high-income settings while approaching CACS' experiences from a biomedical or psychological perspective. However, both perspectives miss an important aspect of survivorship after childhood or adolescent cancer: the affected individual's subjective experiences of having a disabled body. This qualitative study aimed to explore the embodied experiences of Colombian adults who survived cancer during their childhood or adolescence to better understand how CACS relate to their altered body and world. METHODS: By integrating phenomenological insights and conducting comprehensive life-story interviews, we explored the various ways in which survivors' cancer experiences affect their bodily sense of self-from the acute phase of the disease until well into adulthood. A total of ten life-stories interviews and one focus group were carried out with seven CACS. All participants were survivors of a different type of childhood/adolescent cancer. The results were analyzed thematically, focusing on the embodied aspects of participants' experiences. RESULTS: We developed three main themes regarding the embodied cancer experience among participating CACS: Firstly, participants' body changes because of the cancer and its treatment, which makes them aware of their body. Secondly, they adapt to this experience in different bodily ways. Finally, they carry bodily traces of their cancer experience in the present as well as into the future. CONCLUSIONS: The CACS participating in this study report that their experience with cancer has been embodied throughout their lives, changing their sense of their body and how they relate to it, and leaving traces into the present and their imagined future.

Perceived Executive Functioning Deficits After Diagnosis in Women with Non-Metastatic Breast Cancer Prior to Adjuvant Therapies.

BACKGROUND: Perceived deficits in executive functioning are among the many difficulties that women diagnosed with breast cancer experience. This study assessed the presence of perceived deficits in executive functioning among women with breast cancer prior to systemic treatment and radiation and associations between perceived deficits in executive function and comorbid fatigue, sleep, and mood disturbance. METHOD: Participants were recruited following their breast cancer diagnosis and assessed using the Behavior Rating Inventory of Executive Function for Adults (BRIEF-A), subjective and objective measures of sleep duration and efficiency, and self-report measures of insomnia severity, sleep quality, fatigue, and mood disturbance. Hierarchical regression was used to examine associations between symptoms, adjusting for age and education. RESULTS: The final sample included 92 women with a mean age of 60.7 years and 13.5 years of education. Thirteen percent of participants reported global executive dysfunction. After partitioning out variability from other independent variables, fatigue (p = < .001), perceived sleep quality (p = .030), and symptoms of insomnia (p = .008) accounted for 13.3%, 5.7%, and 8.5% of unique variance in perceived executive functioning, respectively. Emotional fatigue was most strongly associated with perceived deficits in executive functioning. Neither subjective or objective sleep duration or efficiency was associated with perceived deficits in executive functioning. CONCLUSION: Fatigue, particularly emotional fatigue, insomnia, and poor sleep quality had the strongest associations with perceived deficits in executive functioning. Sleep interventions and fatigue management strategies may prove useful for women who seek to improve their perceived executive functioning.

End of Life in Patients With Advanced Non-curable Cancer: Patient Considerations Around the Moment of Death.

There is limited knowledge regarding Colombian patients with advanced cancer preferences regarding their final moments, place of death, and post-death wishes. To better understand these preferences, we conducted 23 in-depth interviews with patients between the ages of 28 and 78 receiving treatment at two academic hospitals and the National Cancer Institute. While many participants desired a peaceful death, few were comfortable discussing the topic of death directly. Some younger participants expressed an interest in euthanasia but had not received any guidance or support. While several participants preferred a home death, some expressed a desire to die in a hospital due to better symptom control. Additionally, when discussing post-death wishes, some participants expressed frustration about being unable to have these conversations with their loved ones and their preferences for funeral arrangements. Socioeconomic and geographical factors significantly impacted the wishes and preferences expressed, with many individuals hesitant to initiate difficult conversations.

Prevalence of Cardiovascular Disease and Comorbid Risk Factors in Patients in Puerto Rico with Schizophrenia.

OBJECTIVE: The mortality rate of schizophrenia patients is higher than that of the general population; cardiovascular disease (CVD) is their leading cause of death. This issue must be studied since people with schizophrenia are disproportionately burdened with CVD. Therefore, our goal was to identify the prevalence of CVD and other comorbidities, stratified by age and gender, in patients with schizophrenia living in Puerto Rico. METHODS: A retrospective, case-control, descriptive study was conducted. Subjects in this study were admitted to Dr. Federico Trilla's hospital from 2004 through 2014 for both psychiatric- and non psychiatric conditions. The sample populations were stratified by the confounding variables of tobacco use and alcohol abuse, and the resulting stratification was analyzed with the Cochran-Mantel-Haenszel method. RESULTS: A higher frequency of CVDs was noted in the patients with schizophrenia compared to those in the control group. Although hypertension was the most frequent pathology encountered in both groups, ischemic heart disease was approximately four times more frequent in the patients with schizophrenia. CVD represented 58.4% and 52.7% in the schizophrenia and non-schizophrenia groups, respectively, although a statistically significant difference was not observed. The prevalence of malignancies in patients without schizophrenia was higher than in patients with schizophrenia. Moreover, the prevalence of asthma was 10.9% in the control group compared to 5.3% in the schizophrenia group. CONCLUSION: These findings should motivate a systematic approach to prioritizing the aggressive management, early diagnosis, and prevention of comorbid risk factors in patients with schizophrenia.

Impact of Disease Activity and Inflammatory Bowel Disease Subtype on Quality of Life in Preconception and Pregnant Patients.

BACKGROUND: Inflammatory bowel disease (IBD) and pregnancy both impact health-related quality of life (HRQoL). However, little is known about IBD-related HRQoL around pregnancy. AIMS: To assess the trajectory and predictors of HRQoL in preconception and pregnant patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Preconception and pregnant patients with IBD were followed prospectively from preconception to twelve months postpartum at a tertiary referral centre. Participants completed the Short IBD Questionnaire (SIBDQ) and were assessed for clinical disease activity (modified Harvey Bradshaw Index or partial Mayo score) and objective disease activity (C-reactive protein [CRP], fecal calprotectin [FCP]). RESULTS: A total of 61 patients with IBD (25 CD, 36 UC) were included. During preconception, patients with UC had higher SIBDQ bowel and social sub-scores than those with CD, but this reversed during postpartum. Patients with CD but not UC developed a significant, sustained improvement in SIBDQ upon becoming pregnant, which persisted into 12 months postpartum. In a multivariable linear regression model, clinical disease activity negatively predicted SIBDQ at every pregnancy timepoint and up to 12 months postpartum. SIBDQ was significantly lower in patients with CRP ≥ 8.0 mg/L during trimester 1 (T1), but not later in pregnancy. SIBDQ bowel sub-scores were significantly lower in patients with FCP ≥ 250 mg/kg at T2, T3, and 6 months postpartum. CONCLUSIONS: Clinical disease activity is a consistent negative predictor of HRQoL from conception to 12 months postpartum. Patients with UC experience better preconception HRQoL but suffer worse postpartum HRQoL than those with CD.

Loss of p19Arf promotes fibroblast survival during leucine deprivation.

Fibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation. Since the p19 Alternative reading frame (p19Arf) tumor suppressor is a key regulator of p53 activation during oncogenic stress, we investigated the role of p19Arf in fibroblasts during nutrient deprivation. Here, we show that prolonged leucine deprivation results in increased expression and nuclear localization of p19Arf, triggering apoptosis in primary murine adult lung fibroblasts (ALFs). In contrast, the absence of p19Arf during long-term leucine deprivation resulted in increased ALF proliferation, migration and survival through upregulation of the Integrated Stress Response pathway and increased autophagic flux. Our data implicates a new role for p19Arf in response to nutrient deprivation. This article has an associated First Person interview with the first author of the paper.

Autotrasplante Dental Utilizando Simulación Virtual y un Prototipo de Modelo de Impresión 3D

RESUMEN: La técnica de autotrasplante dental se ideó como opción terapéutica ante la pérdida o ausencia de dientes por traumatismos, caries, agenesias, exfoliación temprana, iatrogenias, u otros factores. Consiste en extraer un diente desde su posición original para implantarlo en un solo acto quirúrgico en una zona edéntula, sea ésta un alveolo postextracción o alveolo confeccionado quirúrgicamente. Un resultado exitoso, requiere una meticulosa selección de candidatos, para esto, se debe considerar la ausencia de patologías y condiciones de orden local o sistémico que dificulten una adecuada cicatrización de heridas y reparación tisular. Nuevas herramientas para facilitar éxito clínico, como la planificación y simulación virtual, junto con la impresión de prototipos en tres dimensiones (3D), permitirían optimizar posibles osteotomías y una implantación del diente donante de manera fácil y en tiempos quirúrgicos mínimos, favoreciendo la disminución de la complejidad quirúrgica, además de la reparación y regeneración de tejidos pulpares y periodontales. El objetivo de este artículo es reunir una serie de consideraciones para optimizar la técnica de autotrasplante dental.

ABSTRACT: The dental autotransplantation technique was devised as a therapeutic option for the loss or absence of teeth due to trauma, caries, agenesis, early exfoliation, iatrogenesis, or other factors. It consists of extracting a tooth from its original position to implant it in a single surgical act in an edentulous area, be it a post-extraction socket or a surgically made socket. A successful result requires meticulous selection of candidates, for this, the absence of pathologies and local or systemic conditions that hinder adequate wound healing and tissue repair must be considered. New tools to facilitate clinical success,such as planning and virtual simulation, together with the printing of prototypes in three dimensions (3D), would allow possible osteotomies and an implantation of the donor tooth in an easy way and in minimal surgical times, favoring the decrease of surgical complexity, in addition to the repair and regeneration of pulp and periodontal tissues. The objective of this article is to gather a series of considerations to optimize the dental autotransplantation technique.

Factors associated with cognitive impairment during the first year of treatment for nonmetastatic breast cancer.

BACKGROUND: Women with breast cancer are more likely to develop cognitive impairment (CI), insomnia, fatigue, and mood disturbance than individuals with other cancers. The main objectives of this study were to establish the prevalence of CI and examine the relationships between CI, insomnia, fatigue, and mood over the first year of breast cancer treatment. METHODS: Participants were recruited after diagnosis and completed validated measures of insomnia, objective and perceived CI, fatigue, and mood disturbance at four time points during the first year of treatment. A random intercepts cross-lagged panel model assessed relationships among symptoms over time. RESULTS: The sample included 98 women. Prevalence of objective CI ranged from 3.1% to 8.2% throughout the year, whereas 36.7% demonstrated a clinically meaningful decline in perceived CI from baseline to 4 months, which remained relatively stable. Greater perceived CI was associated with more fatigue (ß = -0.78, z = 17.48, p < .01) and symptoms of insomnia (ß = -0.58, z = 5.24, p < .01). Short-term fluctuations in perceived CI (p < .05), but not fatigue or insomnia, predicted future perceived CI. Fatigue (p < .001) was a significant predictor of future reported symptoms of fatigue and insomnia. CONCLUSION: Subjective CI is more prevalent than objective impairments. Fatigue, insomnia, and perceived CI remain stable and are associated during the first year of treatment. Changes in insomnia and fatigue may have little effect on future perceived cognition. Women with breast cancer likely require targeted intervention for these side effects.

Bilateral hypopyon in syphilitic uveitis.

PURPOSE: To report an atypical bilateral hypopyon presentation of syphilitic uveitis. OBSERVATIONS: A 38-year-old male presented with a 2-day history of bilateral progressive visual loss, conjunctival hyperemia, and photophobia. Initial ophthalmologic examination revealed bilateral hypopyon and vitritis that limited the examination of the posterior segment. The physical exam revealed cervical lymphadenopathy, glossal leukoplakia, erythematous maculae on the hard palate, erythematous macular lesions on both palms, onychodystrophy, onycholysis, and psoriasiform plaques on both plantar surfaces, testicular tenderness, and hypopigmented patches on the scrotal and perianal skin. A therapeutic and diagnostic vitrectomy was performed on the right eye, and the intraoperative findings were consistent with severe vitritis and pre-retinal precipitates. The cytopathologic analysis of the right vitreous revealed a mixed inflammatory process composed of lymphocytes, histiocytes, and neutrophils in a proteinaceous background. Laboratory testing revealed positive serum RPR, CSF FTA-Abs and VDRL, and HIV serology. Treatment with a 2-week course of intravenous penicillin G 4 million units every 4 hours and topical corticosteroids resulted in complete resolution of the uveitis. CONCLUSIONS AND IMPORTANCE: Bilateral hypopyon uveitis may be a rare presentation of syphilitic uveitis. As with most forms of uveitis, syphilis should be considered in the differential diagnosis of patients presenting with bilateral hypopyon.

Aumento óseo horizontal utilizando técnica "Tent Pole" en mandíbula posterior / Horizontal augmentation using "Tent Pole" technique in posterior mandible

Los aumentos óseos previo a la instalación de implantes son cada vez mas utilizados y el diseño de nuevas estrategias para disminuir la morbilidad deben ser considerados. El objetivo de esta investigación fue definir el aumento óseo generado con la técnica "tent pole" en sector de mandíbula posterior. Se diseño un estudio longitudinal, prospectivo para estudiar la técnica. Se incluyeron sujetos con ancho óseo no mayor a 4 mm en el sector posterior y con altura no menor a 9 mm desde el margen superior del conducto alveolar inferior. Se realizaron cirugías bajo anestesia local realizando un acceso quirúrgico; se instalaron de 2 a 4 tornillos de osteosíntesis manteniendo 4 mm del tornillo extraóseo para luego reconstruir con biomaterial alógeno y L-PRF en conjunto con una membrana biológica absorbible; después de 4 meses se realizaron las re entradas estableciendo con tomografía computadorizada de haz cónico las ganancias óseas generadas. Fueron operados 14 sujetos con 27 sitios quirúrgicos; en todos los casos se pudo realizar la instalación de implantes a los 4 meses. En la evaluación inicial, el ancho óseo observado estaba entre 1,2 y 4,0 mm (promedio de 2,95 ± 0,75 mm); después de 4 meses de realizado el aumento horizontal el ancho observado fue de 3,79 y 10,05 mm (promedio de 7,15 mm ± 1,87 mm), confirmando una ganancia ósea promedio de 4,2 ± 1,26 mm. La diferencia obtenida fue significativa (p< 0,05). Se puede concluir que la técnica "tent pole" aplicada en esta investigación es predecible en el aumento óseo y aplicable para la rehabilitación sobre implante.

Bone augmentation prior to implant placement, is among strategies that should be considered to reduce morbidity rates in these procedures. The objective of this research was to define bone augmentation generator using the "tent pole " technique in the posterior jaw. A longitudinal, prospective study was designed, and subjects were included with ridge width no greater than 4 mm, height no less than 9 mm from the upper margin of the inferior alveolar canal. Surgeries were performed under local anesthesia for surgical approach; 2 to 4 osteosynthesis screws over ridge with 4 mm of the extra osseous screws were installed and were then regenerated, using allogeneic biomaterial and L-PRF together with an absorbable biological membrane. Re-entry was performed after four months and cone beam computed tomography analysis was used to confirm bone gain. Fourteen subjects were operated with 27 surgical sites; in all the cases, implant installation was possible at 4 months. In the initial evaluation, bone width observed was between 1.2 and 4.0 mm (average of 2.95 ± 0.75 mm); after 4 months of the horizontal increase, width was recorded at 3.79 and 10.05 mm (average of 7.15 mm ± 1.87 mm), confirming an average bone increase of 4.2 ± 1.26 mm. The difference obtained was significant (p <0.05). It can be concluded that the "tent pole" technique applied in this analysis is predictable in bone augmentation and applicable for implant rehabilitation.

Functional assessment and treatment of perseverative speech about restricted topics in an adolescent with Asperger syndrome.

A functional analysis showed that a 14-year-old boy with Asperger syndrome displayed perseverative speech (or "restricted interests") reinforced by attention. To promote appropriate speech in a turn-taking format, we implemented differential reinforcement (DR) of nonperseverative speech and DR of on-topic speech within a multiple schedule with stimuli that signaled the contingencies in effect and who was to select the topic. Both treatments reduced perseverative speech, but only DR of on-topic speech increased appropriate turn taking during conversation. Treatment effects were maintained when implemented by family members and novel therapists.

Elevated neutrophil gelatinase-associated lipocalin contributes to erlotinib resistance in non-small cell lung cancer.

PURPOSE: The EGFR tyrosine kinase inhibitors (TKIs) demonstrate efficacy in NSCLC patients whose tumors harbor activating EGFR mutations. However, patients who initially respond to EGFR TKI treatment invariably develop resistance to the drugs. Known mechanisms account for approximately 70% of native and acquired EGFR TKI resistance. In the current study we investigated a novel mechanism of NSCLC resistance to erlotinib. EXPERIMENTAL DESIGN: The mechanisms of acquired erlotinib resistance were evaluated by microarray analysis in thirteen NSCLC cell lines and in vivo in mice. Correlations between plasma neutrophil gelatinase associated lipocalin (NGAL) levels, erlotinib response and the EGFR mutational status were assessed in advanced stage NSCLC patients treated with erlotinib. RESULTS: In 5 of 13 NSCLC cell lines NGAL was significantly upregulated. NGAL knockdown in erlotinib-resistant cells increased erlotinib sensitivity in vitro and in vivo. NGAL overexpression in erlotinib-sensitive cells augmented apoptosis resistance. This was mediated by NGAL-dependent modulation of the pro-apoptotic protein Bim levels. Evaluation of the plasma NGAL levels in NSCLC patients that received erlotinib revealed that patients with lower baseline NGAL demonstrated a better erlotinib response. Compared to patients with wild type EGFR, patients with activating EGFR mutations had lower plasma NGAL at baseline and weeks 4 and 8. CONCLUSIONS: Our studies uncover a novel mechanism of NGAL-mediated modulation of Bim levels in NSCLC that might contribute to TKI resistance in lung cancer patients. These findings provide the rationale for the further investigations of the utility of NGAL as a potential therapeutic target or diagnostic biomarker.

The inflammatory tumor microenvironment, epithelial mesenchymal transition and lung carcinogenesis.

The inflammatory tumor microenvironment (TME) has many roles in tumor progression and metastasis, including creation of a hypoxic environment, increased angiogenesis and invasion, changes in expression of microRNAs (miRNAs) and an increase in a stem cell phenotype. Each of these has an impact on epithelial mesenchymal transition (EMT), particularly through the downregulation of E-cadherin. Here we review seminal work and recent findings linking the role of inflammation in the TME, EMT and lung cancer initiation, progression and metastasis. Finally, we discuss the potential of targeting aspects of inflammation and EMT in cancer prevention and treatment.

Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation.

The Wnt signaling pathway is critical in normal development, and mutation of specific components is frequently observed in carcinomas of diverse origins. However, the potential involvement of this pathway in lung tumorigenesis has not been established. In this study, analysis of multiple Wnt mRNAs in non-small cell lung cancer (NSCLC) cell lines and primary lung tumors revealed markedly decreased Wnt-7a expression compared with normal short-term bronchial epithelial cell lines and normal uninvolved lung tissue. Wnt-7a transfection in NSCLC cell lines reversed cellular transformation, decreased anchorage-independent growth, and induced epithelial differentiation as demonstrated by soft agar and three-dimensional cell culture assays in a subset of the NSCLC cell lines. The action of Wnt-7a correlated with expression of the specific Wnt receptor Frizzled-9 (Fzd-9), and transfection of Fzd-9 into a Wnt-7a-insensitive NSCLC cell line established Wnt-7a sensitivity. Moreover, Wnt-7a was present in Fzd-9 immunoprecipitates, indicating a direct interaction of Wnt-7a and Fzd-9. In NSCLC cells, Wnt-7a and Fzd-9 induced both cadherin and Sprouty-4 expression and stimulated the JNK pathway, but not beta-catenin/T cell factor activity. In addition, transfection of gain-of-function JNK strongly inhibited anchorage-independent growth. Thus, this study demonstrates that Wnt-7a and Fzd-9 signaling through activation of the JNK pathway induces cadherin proteins and the receptor tyrosine kinase inhibitor Sprouty-4 and represents a novel tumor suppressor pathway in lung cancer that is required for maintenance of epithelial differentiation and inhibition of transformed cell growth in a subset of human NSCLCs.